Mothers against decapentaplegic homolog 5

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Q99717 (SMAD5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 129. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Mothers against decapentaplegic homolog 5
Short name=MAD homolog 5
Short name=Mothers against DPP homolog 5

Alternative name(s):
JV5-1
SMAD family member 5
Short name=SMAD 5
Short name=Smad5
Short name=hSmad5

Gene names

Name:	SMAD5
Synonyms:	MADH5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	465 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-regulated SMAD (R-SMAD).
Subunit structure	May form trimers with the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit and SMURF1. Interacts with SUV39H1 and SUV39H2. Interacts (via MH2 domain) with LEMD3. Interacts with WWP1. Ref.12 Ref.13
Subcellular location	Cytoplasm. Nucleus. Note: Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4.
Tissue specificity	Ubiquitous.
Post-translational modification	Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase. Ref.14 Ref.15 Ref.16 Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin ligase SMURF1.
Sequence similarities	Belongs to the dwarfin/SMAD family. Contains 1 MH1 (MAD homology 1) domain. Contains 1 MH2 (MAD homology 2) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	BMP signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB embryonic pattern specification Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription, DNA-dependent Non-traceable author statement Ref.11. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transforming growth factor beta receptor signaling pathway Non-traceable author statement Ref.10. Source: UniProtKB
Cellular component	cytosol Traceable author statement. Source: Reactome integral to membrane Non-traceable author statement Ref.11. Source: UniProtKB transcription factor complex Inferred from electronic annotation. Source: InterPro
Molecular function	sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Traceable author statement. Source: BHF-UCL ubiquitin protein ligase binding Inferred from physical interaction. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed Ref.7

Chain

2 – 465

464

Mothers against decapentaplegic homolog 5

PRO_0000090865

Regions

Domain

13 – 137

125

MH1

Domain

271 – 465

195

MH2

Compositional bias

40 – 46

Poly-Lys

Amino acid modifications

Modified residue

N-acetylthreonine Ref.7

Modified residue

133

Phosphoserine Ref.15

Modified residue

462

Phosphoserine Ref.16

Modified residue

463

Phosphoserine Ref.14 Ref.16

Modified residue

465

Phosphoserine Ref.14 Ref.16

Experimental info

Mutagenesis

419

G → S: Loss of phosphorylation. Ref.5

Sequence conflict

175

D → H in AAC50791. Ref.1

Sequence conflict

237

N → P in AAC50791. Ref.1

Sequence conflict

293

S → R in AAC50791. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

Q99717 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 4A1FD7EC7BD06728
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FASTA

465

52,258

        10         20         30         40         50         60 
MTSMASLFSF TSPAVKRLLG WKQGDEEEKW AEKAVDALVK KLKKKKGAME ELEKALSSPG 

        70         80         90        100        110        120 
QPSKCVTIPR SLDGRLQVSH RKGLPHVIYC RVWRWPDLQS HHELKPLDIC EFPFGSKQKE 

       130        140        150        160        170        180 
VCINPYHYKR VESPVLPPVL VPRHNEFNPQ HSLLVQFRNL SHNEPHMPQN ATFPDSFHQP 

       190        200        210        220        230        240 
NNTPFPLSPN SPYPPSPASS TYPNSPASSG PGSPFQLPAD TPPPAYMPPD DQMGQDNSQP 

       250        260        270        280        290        300 
MDTSNNMIPQ IMPSISSRDV QPVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT 

       310        320        330        340        350        360 
DPSNNKSRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD SSIFVQSRNC 

       370        380        390        400        410        420 
NFHHGFHPTT VCKIPSSCSL KIFNNQEFAQ LLAQSVNHGF EAVYELTKMC TIRMSFVKGW 

       430        440        450        460 
GAEYHRQDVT STPCWIEIHL HGPLQWLDKV LTQMGSPLNP ISSVS

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mad-related genes in the human." Riggins G.J., Thiagalingam S., Rosenblum E., Weinstein C.L., Kern S.E., Hamilton S.R., Willson J.K.V., Markowitz S.D., Kinzler K.W., Vogelstein B.V. Nat. Genet. 13:347-349(1996) [PubMed: 8673135] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Localization of SMAD5 and its evaluation as a candidate myeloid tumor suppressor." Hejlik D.P., Kottickal L.V., Liang H., Fairman J., Davis T., Janecki T., Sexton D., Perry W. III, Tavtigian S.V., Teng D.H., Nagarajan L. Cancer Res. 57:3779-3783(1997) [PubMed: 9288787] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"Smad5, a tumor suppressor candidate at 5q31.1, is hemizygously lost and not mutated in the retained allele in human leukemia cell line HL60." Zavadil J., Brezinova J., Svoboda P., Zemanova Z., Michalova K. Leukemia 11:1187-1192(1997) [PubMed: 9264367] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"hSmad5 gene, a human hSmad family member: its full length cDNA, genomic structure, promoter region and mutation analysis in human tumors." Gemma A., Hagiwara K., Vincent F., Ke Y., Hancock A.R., Nagashima M., Bennett W.P., Harris C.C. Oncogene 16:951-956(1998) [PubMed: 9484787] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12." Nishimura R., Kato Y., Chen D., Harris S.E., Mundy G.R., Yoneda T. J. Biol. Chem. 273:1872-1879(1998) [PubMed: 9442019] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF GLY-419.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Uterus.
[7]	Bienvenut W.V., Lempens A., Norman J.C. Submitted (OCT-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-16; 34-40; 130-158; 283-306 AND 309-319, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT THR-2, MASS SPECTROMETRY. Tissue: Ovarian carcinoma.
[8]	"TGF-beta signal transduction." Massague J. Annu. Rev. Biochem. 67:753-791(1998) [PubMed: 9759503] [Abstract] Cited for: REVIEW.
[9]	"Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells." Verschueren K., Huylebroeck D. Cytokine Growth Factor Rev. 10:187-199(1999) [PubMed: 10647776] [Abstract] Cited for: REVIEW.
[10]	"The Smad pathway." Wrana J.L., Attisano L. Cytokine Growth Factor Rev. 11:5-13(2000) [PubMed: 10708948] [Abstract] Cited for: REVIEW.
[11]	"TGF-beta signaling by Smad proteins." Miyazono K. Cytokine Growth Factor Rev. 11:15-22(2000) [PubMed: 10708949] [Abstract] Cited for: REVIEW.
[12]	"Suv39h histone methyltransferases interact with Smads and cooperate in BMP-induced repression." Frontelo P., Leader J.E., Yoo N., Potocki A.C., Crawford M., Kulik M., Lechleider R.J. Oncogene 23:5242-5251(2004) [PubMed: 15107829] [Abstract] Cited for: INTERACTION WITH SUV39H1 AND SUV39H2.
[13]	"The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines." Pan D., Estevez-Salmeron L.D., Stroschein S.L., Zhu X., He J., Zhou S., Luo K. J. Biol. Chem. 280:15992-16001(2005) [PubMed: 15647271] [Abstract] Cited for: INTERACTION WITH LEMD3.
[14]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-463 AND SER-465, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-462; SER-463 AND SER-465, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U59913 mRNA. Translation: AAC50791.1. AF010601 mRNA. Translation: AAB66353.1. AF010607 AF010606 Genomic DNA. Translation: AAB92396.1. U73825 mRNA. Translation: AAB95090.1. AF009744 AF009743 Genomic DNA. Translation: AAB82655.1. AF009678 mRNA. Translation: AAB72180.1. BC009682 mRNA. Translation: AAH09682.1.
IPI	IPI00017730.
RefSeq	NP_001001419.1. NM_001001419.1. NP_001001420.1. NM_001001420.1. NP_005894.3. NM_005903.5.
UniGene	Hs.167700.
3D structure databases
ProteinModelPortal	Q99717.
SMR	Q99717. Positions 10-133, 270-453.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1180224.
STRING	Q99717.
PTM databases
PhosphoSite	Q99717.
Polymorphism databases
DMDM	13959566.
Proteomic databases
PRIDE	Q99717.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000398807; ENSP00000381787; ENSG00000113658. ENST00000405587; ENSP00000384803; ENSG00000113658. ENST00000419332; ENSP00000410816; ENSG00000113658.
GeneID	4090.
KEGG	hsa:4090.
Organism-specific databases
CTD	4090.
GeneCards	GC05P135496.
H-InvDB	HIX0005199.
HGNC	HGNC:6771. SMAD5.
MIM	603110. gene.
neXtProt	NX_Q99717.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18942.
HOGENOM	HBG443554.
HOVERGEN	HBG053353.
InParanoid	Q99717.
OrthoDB	EOG4HDSTH.
Enzyme and pathway databases
Pathway_Interaction_DB	bmppathway. BMP receptor signaling.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q99717.
Bgee	Q99717.
CleanEx	HS_SMAD5.
Genevestigator	Q99717.
GermOnline	ENSG00000113658. Homo sapiens.
Family and domain databases
InterPro	IPR013790. Dwarfin. IPR003619. MAD_homology1_Dwarfin-type. IPR013019. MAD_homology_MH1. IPR017855. SMAD_dom-like. IPR001132. SMAD_dom_Dwarfin-type. IPR008984. SMAD_FHA_domain. [Graphical view]
Gene3D	G3DSA:3.90.520.10. MAD_MH1. 1 hit. G3DSA:2.60.200.10. MH2_Dwarfin-type. 1 hit.
KO	K04676.
PANTHER	PTHR13703. Dwarfin. 1 hit.
Pfam	PF03165. MH1. 1 hit. PF03166. MH2. 1 hit. [Graphical view]
SMART	SM00523. DWA. 1 hit. SM00524. DWB. 1 hit. [Graphical view]
SUPFAM	SSF56366. MAD_MH1. 1 hit. SSF49879. SMAD_FHA. 1 hit.
PROSITE	PS51075. MH1. 1 hit. PS51076. MH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	16034.
SOURCE	Search...

Entry information

Entry name

SMAD5_HUMAN

Accession

Primary (citable) accession number: Q99717
Secondary accession number(s): O14688, Q15798, Q9UQA1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 4, 2001
Last sequence update:	May 1, 1997
Last modified:	January 25, 2012
This is version 129 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents